Abstract

Introduction Dexterity is described as coordinated hand and finger movement for precision tasks. It is essential for day-to-day activities like computer use, writing or buttoning a shirt. Integrity of brain motor networks is crucial to properly execute these fine hand tasks. When these networks are damaged, interventions to enhance recovery are frequently accompanied by unwanted side effects or limited in their effect. Non-invasive brain stimulation (NIBS) are postulated to target affected motor areas and improve hand motor function with few side effects. However, the results across studies vary, and the current literature does not allow us to draw clear conclusions on the use of NIBS to promote hand function recovery. Therefore, we developed a protocol for a systematic review and meta-analysis on the effects of different NIBS technologies on dexterity in diverse populations. This study will potentially help future evidence-based research and guidelines that use these NIBS technologies for recovering hand dexterity.

Methods and analysis This protocol will compare the effects of active versus sham NIBS on precise hand activity. Records will be obtained by searching relevant databases. Included articles will be randomised clinical trials in adults, testing the therapeutic effects of NIBS on continuous dexterity data. Records will be studied for risk of bias. Narrative and quantitative synthesis will be done.

Strengths and limitations of this study

This is a novel systematic review and meta-analysis focusing specifically on dexterity.

We use continuous data not dependent on the evaluator or participant.

This work will potentially help future evidence-based research and guidelines to refine non-invasive brain stimulation.

Introduction

The hand’s somatotopy is extensively represented in the human motor cortex.1 2 Phylogenetically, this relates to the development of corticomotoneuronal cells that specialise in creating patterns of muscle activity that synergises into highly skilled movements.3 This organised hand-and-finger movement to use objects during a specific task is known as dexterity.4 Evolutionary, dexterity played a pivotal role in human survival and is fundamental to actives of daily living, and hence quality of life.5 6

This precision motor movement relies on integration of information from the cerebral cortex, the spinal cord, several neuromusculoskeletal systems and the external world to coordinate finger force control, finger independence, timing and sequence performance.7 During these tasks, multivoxel pattern decoding shows bilateral primary motor cortex activation (M1), which was responsible for muscle recruitment timing and hand movement coordination.8 9 This is related to motor cortex connectivity through the corpus callosum, to motor regions of the cerebellum and white matter integrity.10–15 Adequate motor output translates into successfully executed tasks, like picking up objects, turning over cards, manipulating cutlery, writing, using computer–hand interfaces like smartphones, playing an instrument and performing many other similarly precise skills.16

These motor tasks are negatively impacted when motor output networks are affected, as seen in stroke or Parkinson’s disease.17 18 Therapeutic interventions that restore these damaged motor networks can be vital to restore fine motor movement after injury occurs. Pharmaceutical approaches often lead to adverse effects such as dyskinesias in Parkinson’s disease. Moreover, even after intensive rehabilitation programmes, only about 5%–20% of patients with stroke fully recover their motor function.19–21 Non-invasive brain stimulation (NIBS) techniques, like transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), are proposed adjuvant or stand-alone interventions to target these affected areas and improve fine motor function.22 23 Briefly, these NIBS interventions are shown to influence the nervous system’s excitability and modulate long-term plasticity, which may be beneficial to the brain’s recovery of functions after injury.24–27

Fine hand motor ability is not studied as much in previous reviews of NIBS. Specifically, one narrative review focuses on rTMS in affected hand recovery poststroke; however, it does not consider the implications of varying International Classification of Functioning, Disability and Health (ICF) domains, data types and rater dependent outcomes, and its interpretability is limited without quantitative synthesis.28–31 The overarching conclusion was supportive of rTMS for paretic hand recovery, though with limited data to support its regular use, and a pressing need to study individualised patient parameters.28 One meta-analysis had positive and significant results when specifically studying the effects of rTMS on finger coordination and hand function after stroke.32 However, while various meta-analysis, and another systematic review, studied upper-limb movement after NIBS in distinct populations, they did not focus on precise hand function, pooled upper-limb outcomes with hand outcomes and presented mixed results.33–38

Motivated by this gap in the evidence for NIBS in dexterity, we will do a systematic review and meta-analysis of the literature on these brain stimulation technologies using outcomes that focus exactly on manual dexterity. These outcomes will be continuous and not dependent on the participant’s or rater’s observation (ie, they will be measured in seconds, or number of blocks/pegs placed, and not by an individual’s interpretation). They will be comprised of multiple domains as defined by the ICF, providing an appreciation of function rather than only condition or disease.29–31 By focusing on the ICF model, we will be able to study dexterity across a larger sample of studies, NIBS techniques and conditions in order to provide a better understanding of brain stimulation efficacy on hand function in various populations.[…]

Motor practice is an essential part of upper limb motor recovery following stroke. To be effective, it must be intensive with a high number of repetitions. Despite the time and effort required, gains made from practice alone are often relatively limited, and substantial residual impairment remains. Using non-invasive brain stimulation to modulate cortical excitability prior to practice could enhance the effects of practice and provide greater returns on the investment of time and effort. However, determining which cortical area to target is not trivial. The implications of relevant conceptual frameworks such as Interhemispheric Competition and Bimodal Balance Recovery are discussed. In addition, we introduce the STAC (Structural reserve, Task Attributes, Connectivity) framework, which incorporates patient-, site-, and task-specific factors. An example is provided of how this framework can assist in selecting a cortical region to target for priming prior to reaching practice poststroke. We suggest that this expanded patient-, site-, and task-specific approach provides a useful model for guiding the development of more successful approaches to neuromodulation for enhancing motor recovery after stroke.

Poststroke Arm Impairment

Upper limb motor impairment following stroke is highly prevalent and often persists even after intensive rehabilitation efforts (1–4). It is also one of the most disabling of stroke sequela, limiting functional independence and precluding return to work and other roles (5).

Upper extremity motor control relies heavily on input transmitted via the corticospinal tract (CST). The CST descends through the posterior limb of the internal capsule, an area vulnerable to middle cerebral artery stroke and in which CST fibers are densely packed. Thus, even a small lesion in this location can have devastating effects on motor function (6–9). A loss of voluntary wrist and finger extension is particularly common and appears to be related to the extent of CST damage (10). There is also evidence that those who retain wrist extension and have considerable CST sparing are more likely to be responsive to existing therapies (7, 8, 11).

However, even individuals who lack voluntary wrist and finger extension often retain some ability to move the shoulder and elbow. Unfortunately, only a few stereotyped movement patterns can be performed and these are often not functional. The combination of shoulder flexion with elbow extension that is required for most functional reaching tasks, for example, is frequently lost. Nevertheless, previous studies have demonstrated that reaching practice with trunk restraint can improve unconstrained reaching ability, even in patients who lack wrist and finger extension (12–15). Still, a great deal of time and effort is required and the improvements are relatively small.

Non-Invasive Brain Stimulation

Non-invasive brain stimulation offers a potential method of enhancing the effects of practice and thus giving patients greater returns on their investment of time and effort. Approaches to non-invasive brain stimulation are rapidly expanding but generally fall into two major categories: transcranial magnetic stimulation (TMS) and transcranial electrical stimulation [TES; see Ref. (16) for overview of non-invasive techniques for neuromodulation]. These modalities are applied to the scalp overlying a specific cortical area that is being targeted. The level of spatial specificity varies depending on many factors including the modality used (TMS is generally more precise than TES), the stimulation intensity (higher intensity results in a more widespread effect), and the architecture of the underlying tissue. The excitability of the underlying pool of neurons can be modulated by varying stimulation parameters such as the frequency and temporal pattern of the stimuli. Therefore, stimulation can be used to temporarily inhibit or facilitate the underlying cortical area for a sustained period of time after the stimulation ends (usually 20–40 min). In this way, non-invasive brain stimulation could be used to “prime” relevant cortical areas before a bout of practice, potentially enhancing the effects of practice. However, there is little guidance for how such cortical sites might be selected and in which direction (inhibition or facilitation) their activity should be modulated. Conceptual models that could offer such guidance are considered below.

Mechanistic Models to Guide Neuromodulation

Figure 1. On randomly delivered trials, transcranial magnetic stimulation (TMS) perturbation was applied just after a “Go” cue. The effect of this pre-movement perturbation on the speed of the subsequent reaching movement is expressed relative to that in trials with no TMS perturbation. The amount of slowing due to TMS perturbation of the lesioned vs. non-lesioned hemispheres is shown for patients with good structural reserve (left) and patients with poor structural reserve (right).

The brain consists of two hemispheres each responsible for controlling the opposite side of the body. Normally, each hemisphere inhibits the opposite side to avoid mirror movements (both sides performing same movement simultaneously).

After a stroke, the two hemispheres experience an unbalancing of both sides with the unaffected hemisphere receiving more signals than the affected hemisphere. This imbalance leads to increased excitability and decreased inhibition to the healthy side.

Priming is a technique used to enhance the brain’s ability to re-balance the two hemispheres following a stroke. Priming interventions include invasive and non-invasive techniques and can be administered prior to or during recovery.

Stimulate Recovery.

Sensory electrical stimulation using the SaeboStim Micro is an example of a safe, non-invasive technique used to improve cortical excitability of the affected side of the brain. By priming the brain with theSaeboStim Micro, prior to or during functional training, cortical plasticity and rebalancing of the hemispheres may lead to better functional outcomes.

OUR MISSION

The NeuroRehabLab is an interdisciplinary research group of the University of Madeira that investigates at the intersection of technology, neuroscience and clinical practice to find novel solutions to increase the quality of life of those with special needs. We capitalize on Virtual Reality, Serious Games, and Brain-Computer Interfaces to exploit specific brain mechanisms that relate to functional recovery to approach motor and cognitive rehabilitation by means of non-invasive and low-cost technologies.

INTRODUCTION: Most of the stroke survivors do not recover the basal state of the affected upper limb, suffering from a severe disability which remains during the chronic phase of the illness. This has an extremely negative impact in the quality of life of these patients. Hence, neurorehabilitation strategies aim at the minimization of the sensorimotor dysfunctions associated to stroke, by promoting neuroplasticity in the central nervous system.

DEVELOPMENT: Brain reorganization can facilitate motor and functional recovery in stroke subjects. None-theless, after the insult, maladaptive neuroplastic changes can also happen, which may lead to the appearance of certain sensori-motor disorders such as spasticity. Noninvasive brain stimulation strategies, like transcranial direct current stimulation or transcranial magnetic stimulation, are widely used techniques that, when applied over the primary motor cortex, can modify neural networks excitability, as well as cognitive functions, both in healthy subjects and individuals with neurological disorders. Similarly, brain-machine-interface systems also have the potential to induce a brain reorganization by the contingent and simultaneous association between the brain activation and the peripheral stimulation.

CONCLUSION: This review describes the positive effects of the previously mentioned neurorehabilitation strategies for the enhancement of cortical reorganization after stroke, and how they can be used to alleviate the symptoms of the spasticity syndrome.

BACKGROUND: Traumatic brain injury (TBI) is a common cause of physical,psychological, and cognitive impairment, but many current treatments for TBI are ineffective or produce adverse side effects. Non-invasive methods of brain stimulation could help ameliorate some common trauma-induced symptoms.

OBJECTIVE: This review summarizes instances in which repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) have been used to treat symptoms following a TBI. A subsequent discussion attempts to determine the value of these methods in light of their potential risks.

METHODS: The research databases of PubMed/MEDLINE and PsycINFO were electronically searched using terms relevant to the use of rTMS and tDCS as a tool to decrease symptoms in the context of rehabilitation post-TBI.

RESULTS: Eight case-studies and four multi-subject reports using rTMS and sixmulti–subject studies using tDCS were found. Two instances of seizure are discussed.

CONCLUSION: There is evidence that rTMS can be an effective treatment option for some post-TBI symptoms, such as depression, tinnitus, and neglect. Although the safety of this method remains uncertain, the use of rTMS in cases of mild TBI without obvious structural damage may be justified. Evidence on the effectiveness of tDCS is mixed, highlighting the need for additional investigations.

The EBS Therapy is a non-invasive electrical stimulation treatment device that is individually adapted to the patient’s condition in order to restore visual field losses caused by neurological disorders such as stroke, traumatic brain injury (TBI), anterior ischemic optic neuropathy (AION) as well as several types of glaucoma…

METHODS: Five participants with chronic neurologic insult (stroke or traumatic brain injury > 6 months prior) completed 24 sessions (40 minutes, three times/week) of UE-PT combined with bihemispheric tDCS delivered at 1.5 mA over the motor cortex during the first 15 minutes of each PT session. Outcomes were assessed using clinical (UE Fugl-Meyer, Purdue Pegboard, Box and Block, Stroke Impact Scale) and robotic (unimanual and bimanual motor control) measures. Change in scores and associated effects sizes from Pre-test to Post-test and a six month Follow-up were calculated for each participant and group as a whole.

…This review intends to synthesize our understanding of the effects of novel approach of non-invasive peripheral nerve and brain stimulation techniques in motor rehabilitation and the potential role of these techniques in clinical practice. The ability to induce cortical plasticity with non-invasive stimulation techniques has provided novel and exciting opportunities for examining the role of the human cortex during a variety of behaviors literature concerning non-invasive stimulation technique incorporated into stroke research is young, limiting the ability to draw consistent conclusions. In this review we discuss how these techniques can enhance the effects of a behavioral intervention and the clinical evidence for its use to date…